Elevated soluble 4-1BB is associated with serum markers of hepatitis B virus in patients with chronic hepatitis B

Figure 1 Plasma soluble 4-1BB levels in various groups of treatment-naïve patients with chronic hepatitis B (except for the comparison between treatment naïve group and entecavir treated group). A: Soluble 4-1BB (s4-1BB) levels in healthy adults and chronic hepatitis B (CHB); B and C: s4-1BB levels in patients with CHB in various phases of disease (CHB flare means infection exhibiting a disease flare up, elevated alanine aminotransferase; CHB inactive means patients with inactive disease, normal alanine aminotransferase); D: s4-1BB levels before and after treatment in patients with hepatitis B virus; E: Plasma s4-1BB levels in healthy adults and healthy children; F: Plasma s4-1BB levels in healthy male donors and healthy female donors. P values were obtained by the Mann–Whitney U test or unpaired t test according to the characteristics of the data. ^cP < 0.001 vs healthy adult group; ^dP < 0.05 vs chronic hepatitis B inactive group; ^eP < 0.05 vs log₁₀HBV DNA < 5 group. CHB: Chronic hepatitis B; s4-1BB: Soluble 4-1BB; ETV: Entecavir.

Figure 2 Association between plasma soluble 4-1BB levels and hepatitis B virus markers as well as clinical parameters in treatment-naïve patients with chronic hepatitis B. A-C: The positive correlations of plasma soluble 4-1BB (HBsAg) levels with quantitative hepatitis B surface antigen (HBsAg), hepatitis B virus DNA, and hepatitis B e antigen (HBeAg); D-F: The correlations of plasma s4-1BB levels with alanine aminotransferase (ALT), IFNγ, and triglyceride (TG). Correlations were tested by Spearman’s rho (r), and the level of significance was expressed as the P value (P). CHB: Chronic hepatitis B.

Figure 3 Expression of 4-1BB in the peripheral blood mononuclear cells of treatment-naïve patients with chronic hepatitis B and healthy adults. A-C: Soluble 4-1BB (s4-1BB) mRNA levels of peripheral blood mononuclear cells (PBMCs), CD4⁺ T cells, and CD8⁺ T cells in peripheral blood were compared between patients with chronic hepatitis B (CHB) and healthy adults. Horizontal lines indicate the median values ± standard error of the mean, and P values were obtained by the Mann–Whitney U test or unpaired t test according to the characteristics of the data.